Farnesol activates a microsomal cysteine protease with high specificity for HMG CoA reductase (Correll, C. C., et al., J. Biol. Chem. 269:17390-17393, 1994; Meigs, T. E., et al., J. Biol. Chem. 271:7916-7922, 1996). As a consequence, the cellular pool of mevalonic acid becomes limiting for cell proliferation. Neoplastic cells have much greater sensitivity than normal cells to farnesol-mediated actions (Adany, I., et al. Cancer Lett. 79:175-179, 1994; Yazlovitskaya E. M. and Melnykovych, G., Cancer Lett. 88:179-183, 1995).
Diet studies show that farnesol (90 mmol/kg diet) suppressed the growth of pancreatic tumors implanted in Syrian Golden hamsters (Burke, et al., Lipids 32:151-156, 1997). The elevation of farnesol is short-lived as cytosolic prenyl alcohol dehydrogenase and microsomal oxidase activities convert farnesol to xcex1-, xcfx89-prenyl dioic acids which are excreted (Christophe, J. and Popjak, G., J. Lipid Res. 2:244-257, 1961; Gonzalez-Pacanowska, D. G., et al., J. Biol. Chem. 263:1301-1306, 1988). He, et al. (He, L., et al., J. Nutr. 127:668-674, 1997) reported findings that xcex3-tocotrienol, a farnesol mimetic, suppressed the growth of implanted melanomas with nearly 100xc3x97greater efficacy than farnesol ( less than 1 mmol/kg diet). When coupled with the tocol ring the farnesyl moiety is not converted to the prenyl acids and thus is not excreted.
In one embodiment, the present invention is a method of suppressing the growth of tumor cells in a patient, comprising treating the patient with an effective amount of an isoprenoid ether-linked compound, wherein the isoprenoid ether-linked compound comprises a first acyclic isoprenoid molecule linked via an ether linkage to a second molecule, wherein the second molecule can suppress tumor formation. Preferably, the second molecule comprises a cyclic isoprenoid or hydroxyphenol acetate.
In another embodiment the second molecule is selected from the group consisting of flavonols, isoflavonols and polyphenols and substituted hydroquinones.
In another embodiment, the present invention is a chemotherapeutic compound comprising an acyclic isoprenoid alcohol linked via an ether linkage to a cyclic isoprenoid alcohol or 4-hydroxyphenyl acetate and a pharmaceutical carrier.
In another embodiment, the present invention is a chemotherapeutic compound comprising M364 and a pharmaceutical carrier.
It is a feature of the present invention that a chemotherapeutic compound is provided.
It is an object of the present invention to treat tumor patients by ingestion of an acyclic isoprenoid ether linked compound.
Other objects, features and advantages of the present invention will become apparent to one of skill in the art after review of the specification, claims and drawings.